Dr. Su's long-term career objectives are to identify novel treatments and develop biology-driven, mechanism-specific clinical trials in pediatric neuro-oncology. His current focus is on studying valproic acid and other related histone deacetylase (HDAC) inhibitors as novel treatments for medulloblastomas (MB). Based on his pre-clinical studies, Dr. Su is currently conducting a Phase 1 clinical trial of valproic acid in children with recurrent solid and CNS tumors through the Children's Oncology Group. The major goals of this Phase 1 clinical trial are to document the toxicities and pharmacokinetics of chronic valproic acid administration in children with recurrent tumors and determine the correlation between serum drug concentrations and histone hyper-acetylation, the proposed anti-tumor mechanism. Dr. Su has completed a proposal for a subsequent Phase 2 clinical trial to study valproic acid's efficacy against recurrent pediatric CNS tumors, and this proposal will be submitted to a national cooperative group upon completion of the ongoing Phase 1 clinical trial. Dr. Su and his collaborators have also demonstrated valproic acid's potential in protecting normal brain against radiation-damage, enhancing MBs' radiation sensitivity, and treating minimal residual tumors. Accordingly, Dr. Su plans to initiate a Phase 1 clinical trial to study the safety of administering valproic acid concomitantly with radiation in children newly diagnosed with MBs. If his initial clinical trials showed that valproic acid has promising activities against MBs, Dr. Su will explore the potential for a national cooperative group Phase 3 trial, in which patients receive valproic acid with up-front radiation, complete chemotherapy, and then are randomized to observation versus valproic acid for a year. Dr. Su and his collaborators also plan to evaluate additional HDAC inhibitors, as they may be more potent and less toxic than valproic acid. Another pre-clinical study is planned to evaluate the combined efficacies of temozolomide and a poly (ADP- ribose) polymerase (PARP) inhibitor against pediatric malignant gliomas and MBs. In summary, Dr. Su's has demonstrated early promise in translating molecular discoveries into clinical trials, and he is committed to his career development as an independent clinical researcher in pediatric neuro-oncology.